In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer's disease

Amyloid β (Aβ) deposition in the brain is considered the initiating event in the progression of Alzheimer's disease (AD). Amyloid imaging is widely studied in diagnosing AD and evaluating the disease stage, with considerable advances achieved in recent years. We have developed a novel 19F-containing curcumin derivative (named FMeC1) as a potential imaging agent. This compound can exist in equilibrium between keto and enol tautomers, with the enol form able to bind Aβ aggregates while the keto form cannot. This study investigated whether FMeC1 is suitable as a 19F magnetic resonance imaging (MRI) probe to detect Aβ deposition in the Tg2576 mouse, a model of AD. In 19F nuclear magnetic resonance (NMR) spectra obtained from the whole head, a delayed decreased rate of 19F signal was observed in Tg2576 mice that were peripherally injected with FMeC1 in comparison to wild-type mice. Furthermore, 19F MRI displayed remarkable levels of 19F signal in the brain of Tg2576 mice after the injection of FMeC1. Histological analysis of FMeC1-injected mouse brain showed penetration of the compound across the blood–brain barrier and binding to Aβ plaques in peripherally injected Tg2576 mice. Moreover, the distribution of Aβ deposits in Tg2576 mice was in accordance with the region of the brain in which the 19F signal was imaged. FMeC1 also exhibited an affinity for senile plaques in human brain sections. These findings suggest the usefulness of FMeC1 as a 19F MRI probe for the detection of amyloid deposition in the brain. Furthermore, the properties of FMeC1 could form the basis for further novel amyloid imaging probes.

▶ We have developed FMeC1 as a novel 19F MR probe for detecting Aβ deposition. ▶FMeC1 showed BBB permeability and an affinity to Aβ plaques in Tg2576 mouse. ▶Marked levels of 19F signal were detected in the brain of FMeC1-injected Tg2576 mice. ▶The regions of the 19F signals were consistent with those containing Aβ deposits. ▶19F MRI with FMeC1 is beneficial as a novel method for detecting Aβ deposition.